Acne vulgaris affects virtually all youngsters beginning at the age of about 13 years and continuing through the age of 23 years. In females the onset may occur at an age as early as 10 or later on in the 20's or 30's. As is evident from all of the media, this affliction is sufficiently frequent and the mental suffering, particularly, sufficiently severe so that many companies vie for the resultant market for appropriate medications. The number of anti-acne products sold over the counter and by prescription is enormous.
Many compounds and compositions have been tested and prescribed for the disease and a number have been fairly effective, but, as yet, there has been no complete cure for acne.
Therapy is extremely important since if acne is left untreated, cysts form which result in permanent pitting and disfiguring scarring. Moreover, since acne is a disease primarily of adolescence, when the sufferers are most uncertain of themselves in their new roles, the attendant stigma, both supposed and real, can be the source of severe psychological trauma.
There appears to be no doubt but that the increased flow of hormones at the onset of and during adolescence is the primary etiologic agent, since these hormones increase the size of the sebaceous glands and increase the secretion produced by these glands. However, no correlation has been found between the amount of endogenous serum hormone levels and the severity of acne in the individual.
The sebaceous glands which are present in the dermal layer of the skin produce sebum. These glands are concentrated particularly on the face, upper torso including both the chest and back, and on the scalp. Susceptibility to acne is usually greatest on the nose and on the face.
As the sebum is produced it normally flows slowly onto the surface of the skin. When the ducts through which the sebum flows are blocked, the sebum cannot reach the surface of the skin so that pressure builds up in the ducts and the ductal wall ruptures, allowing the sebum to seep into the skin's dermal layers, causing inflammation. Applying pressure to the inflamed area spreads the sebum into the dermal tissue and spreads the inflammation over a wider area.
The sebum is broken down by microorganisms which are normally present in and on the skin, the principal microorganism being C. acnes. This microorganism produces lipase enzymes which hydrolyze the triglycerides of the sebum, forming the free fatty acids which are responsible for the externally visible comedones. The plug formed when a sebaceous duct is blocked is called a "comedo". The comedo itself is a noninflammatory lesion consisting of lipid and keratin. The lesions may initiate as papules which in turn may evolve into pustules. However, the lesions may also be in the form of deeper nodules which enlarge into cysts.
Diet was originally considered to be one of the principal factors responsible for acne, the other being a lack of complete cleanliness. Chocolate was frequently considered the major villain, but recent studies have shown that neither strict prohibition of suspected foods nor strict hygienic cleansing of the skin gives the desired elimination of acne.
With the recognition of the fact that bacteria were responsible, treatment with antibiotics became popular, tetracycline being the drug of choice. However, the degree of improvement produced by the use of any of the antibiotics was so small that it was frequently unrecognizable. Treatment with sulphur lotions has a long history but, again, this material by itself failed to produce substantial improvement of the condition.
Complicating this situation has been the fact that young women, particularly, resort to the use of cosmetics, many of which, despite claims to the contrary, proved to be severely comedogenic. Increase in the severity of the acne caused by cosmetics then leads to the use of similar materials as covering agents, further exacerbating the condition.
A. M. Kligman in work carried out in cooperation with James E. Fulton, Jr. discovered that peeling of the skin induced by topical application of Vitamin A acid, also called retinoic acid was beneficial in the treatment of acne, and U.S. Pat. No. 3,729,568 issued to Kligman in 1973. Approximately simultaneously, the effect of topical application of benzoyl peroxide was also investigated and it was found that the treatment was relatively effective. U.S. Pat. No. 3,535,422 entitled "Stable Benzoyl Peroxide Composition" issued to Richard M. Cox and Leonard R. Clufo in 1970.
The effectiveness of benzoyl peroxide in the treatment of acne proved to be a function of the stability of the composition applied to the affected region. Cox et al taught that dispersing benzoyl peroxide in a fluid medium consisting only of water and organic emollients produced a substantially inert, stable composition. This stability is necessary if the product is to have a reasonable shelf-life, either in the pharmacy or in the family medicine chest. However, as will be shown below, benzoyl peroxide compositions prepared in accordance with any of the formulations heretofore available decompose rapidly during storage. Decomposition of the benzoyl peroxide when in contact with the skin is desirable since it is the oxidizing effect of the free radicals produced on decomposition which provides the desired effect. However, decomposition during storage severely reduces the effectiveness of a composition which is prepared so that it has initially the optimum concentration.
As is evident, then, a composition in which the benzoyl peroxide is stable during storage and yet decomposes readily on contact with the skin would be highly desirable, as would be a method of treatment based on such a composition. Moreover, other organic peroxides have also been found to be effective for the treatment of acne and some of these are even more unstable during storage than is benzoyl peroxide. It would also be desirable that a means of contributing stability of such peroxides during storage be provided.